LIFECYCLE MANAGEMENT STRATEGIES:
THE GENERIC PERSPECTIVE
Regulatory Affairs Professionals
Society
Horizons Conference
March 29, 2007
Michael A. Swit, Esq.
Vice President, Life Sciences
The Generic View – Defense First;
Offense Second?
• Defending the Future – ensuring time is not
lost to a brand with exclusivity
– Understanding Brand Strategies
•
•
•
•
Patents – not the focus here
Petitions
Reformulations
Formulary Battles
– Fighting Back – see Offense?
2
The Generic View – Defense First;
Offense Second?
• Offense
–
–
–
–
Attacking patents -- not focus of this talk
Attacking a Competitor’s ANDA Exclusivity
Attacking petitions
Carving out unique markets
• ANDA Suitability Petition
• Morphing Into a Brand Name Company
– 505(b)(2) NDAs –
3
Brand Attacks – Where They Occur
• FDA –
– usually in the form of a Citizen Petition linked to a
Petition to Stay approvals
• Buys 180 days almost immediately
• Depending on when filed -- if prior to ANDA
approval-- can cause lengthy delays
• “Safety” – at heart of brand allegations
– Reformulations
4
Brand Attacks – Where They Occur
• The Courts – primarily in the form of
aggressive patent infringement litigation
• The Congress –
– Special interest legislation – occurred more
frequently in Republican Congresses
– Less a factor today
5
Brand Attacks – Where They Occur
• States
– Formularies -- safety issues – often similar to those
raised at the federal level
– Legislatures
• substitution restrictions
• DAW manipulation
6
Brand Attacks – Where They Occur
• Pharmacists
– 1985 letter to pharmacists regarding substituting
propranolol for the patients with the exclusive
indication
– Coumadin -- Barr counterattacked at this level with a
pharmacist education program
7
Brand Attacks – Where They Occur
• HMOs and Other Private Formularies
– Private switch restrictions or incentives to not do so
– Qualifying the generic
• Doctors
– who knows what is being said by the field reps??
8
Citizen Petitions
• The “We are only concerned about safety first”
Attack -- raising a concern about the generic
presenting a higher side effect profile or some other
complication that might affect the patient adversely if
switched to the generic.
– My first encounter -- reformulating out a preservative -1986 before the New Jersey formulary
– Reply: showed adverse events with old formulation were
minor. Generic won.
9
Citizen Petitions – “Safety First”
• Glaxo/Ventolin -– longer term clinical studies need to assess full side effect liability;
claimed that a key FDAer had expressed concerns about possible
paradoxical bronchospasm when small changes made in MDIs.
– 24-patient crossover study does not achieve statistical significance in
detecting a “true difference” in adverse event rates.
– Guidance did not address pediatric use, but the drug is likely to be used
in kids even though not so labeled.
• FDA:
– Assessing side effects is not a direct duty under Waxman-Hatch if
bioequivalence can be proven; here there was a good protocol for
showing it and FDA has discretion on how to prove bioequivalence.
– Did not show any data to prove that there might not be bioequivalence
in kids; implication: if bioequivalent in adults, is in kids
10
Citizen Petitions – “Safety First” …
• Sandoz/Clozapine -- not safe to use healthy
subjects for the bioequivalence study
• FDA: we see no differences in adverse reactions
with healthy v. patients if you use 12.5 mg. dose;
consulted outside medical expert.
11
Citizen Petitions – “Safety First” …
• Marion Merrill Dow/Seldane -- requested FDA require multiple dose
pharmacokinetic/pharmacodynamic crossover study comparing plasma
concentrations of terfenadine, the active metabolite, and QtC changes.
– Allegation: the single-dose study design in FDA bioequivalence guide did not
consider the safety concerns of low levels of parent terfenadine and their
relationship to Qtc prolongation which can cause tachycardia.
• FDA: refused to change the study design, saying that:
– Pharmacokinetic testing is preferred; pharmacodynamic testing “tend to be so
imprecise that statistical criteria can be met only with an unreasonably large
number of subjects.”
– You failed to show us that the pharmacokinetic studies are inadequate or that
what you propose is better.
12
Citizen Petitions -- The ”Your
bioequivalence study does not really
show equivalence” Attack:
•
Boehringer/Persantine -- (90P-0326)
alleged there were deficiencies in bio study done by
BioDecision for Purepac -- primarily that the AUC and CMAX
were significantly higher than other generics that had already
shown bioequivalence
FDA:
•
–
–
–
Not appropriate to make cross-study comparisons of absolute values.
Values observed were derived from study where the assay methodology
was validated, the assay procedure well-controlled, and where the values
achieved were not dissimilar to those achieved by other labs.
Also rejected assertion that the lab here was too deficient to be used.
13
Citizen Petitions -- The “Comparative
clinical trials required to show
bioequivalence” Attack:
•
Fisons/Intal/the nebulizer version (93P-0010) -asked for an in vivo bioequivalence standard requiring
well-controlled clinical trials.
FDA:
•
–
–
here, the key was that the drug met the bioequivalence
regulations (21 CFR Part 320) criteria for a waiver of in
vivo studies as it was in solubized form
also stressed that comparative clinical studies are “the least
accurate, sensitive and reproducible” of the general
approaches to bioequivalence.
14
Citizen Petitions – The “You Must
Have the Same Inactives and Labeling As
Us” Parley
• Diprivan
– Reformulated to use a preservative
– Clinicals – 3-year Waxman-Hatch Exclusivity
– You must use same inactive and, btw, your label contains a
different warning
• FDA
– Selected generic preservative OK
– Different warning reflects “different mfr.” carve-out of
Waxman-Hatch
15
Citizen Petitions -- Others
•
The “Your Generic Sustained Release Must
The Same release mechanism as us to be the
same dosage form” Gambit:
–
–
•
Pfizer/Procardia XL
FDA: release mechanism is not relevant to dosage form
determination.
The “You have to meet the new disso-lution
specification that FDA forced us to meet”
Maneuver
–
Roche/Klonopin -- withdrawn by Roche for unstated
reasons
16
Citizen Petitions – “Winners” -- The
“Active ingredient(s) must be fully
characterized” Parley
•
Wyeth-Ayerst/Premarin -- “full” story on FDA’s
web site
Lovenox – still pending, but has worked for 4 years
– low molecular weight heparin
•
•
•
EU – regards as a biologics
Pergonal – exception, but limited by its facts
–
–
“Different isoforms” did not relate to key structure;
protein backbone and amino acid sequences were
identical
No data to show clinical significance of isoform
differences
17
Citizen Petitions – “Winners” –
Active Ingredient Characterization
• Generic biotech products –
– this parley still forms basis for a prime source of
opposition to efforts to secure regulatory or
legislative solutions to absence of generic biotech
products;
– Even if there is legislation, characterization will
remain a central form of attack to influence FDA’s
discretion
• General Rule – FDA wins in courts on scientific issues
18
Reformulations – The Moving
Target
• The backdrop:
– Waxman-Hatch – ANDA’d drug must be
same as “reference listed drug”
– The Gomer Pyle Syndrome – right before
patent/exclusivity expiry, the formulation
changes [“surprise, surprise, surprise”]
19
Reformulation -- Example
• Tricor (fenofibrate)
– Original NDA – 67 mg & 200 mg. capsules
– Teva sued for patent infringement; 30-month stay
– Abbott reformulated to 54 & 160 mg. tablets
• Pulled capsules
– Abbott reformulated again to 48 & 145 mg. tablets, and
got a label change to remove requirement product be taken
with food
– Teva – was able to approval, but its product was not ABrated to Abbott’s
20
Other “Reformulations”
• Rx-to-OTC Switches
– But, fight back – “forced switch” petitions
• Nexium® -- change to different active
ingredient that is barely different from Prilosec
21
Generic vs. Generic Tactics
• ANDA Suitability Petitions
• ANDA Exclusivity
• Morphing into “Brand Name”
Drug Development
22
ANDA Suitability Petition
• Standard – FDA must approve unless clinical investigations required
• Examples
– Dosage form -- tablet to capsule change
– Strength – usually lower or intermediate if consistent with labeled dosing regimen;
higher – rare
– Route of administration – possible, but rarer
• PPA Patch -- denied
– Ingredient – only a single ingredient in a combination drug
– Different salts – not allowed
• Advantage – product line extension – e.g., Roxane
• Disadvantages
– no exclusivity; anyone else can do same thing; timing is important
– Public process
– Pediatric studies – under PREA – may need to do
23
Elements for ANDA Exclusivity
• First Person to Submit Complete ANDA
(“First to File”)
• Containing a Paragraph IV Certification
• Challenging a Patent as Invalid or Not
Infringed
• Notice to Patent Holder and NDA Holder (if
different)
• Eligible for 180 Days of Exclusivity
24
Medicare Modernization Act of
2003 -- Impact on Exclusivity
• Trigger for Start of Exclusivity
– Before Aug. 18, 2003: Earlier of Date of Favorable Court
Decision in a Patent Lawsuit, or Date of First-to-File’s First
Commercial Marketing
– After Aug. 18, 2003: First-to-File’s First Commercial Marketing
(Only)
• Timing of Notice to NDA/Patent Holder
– Before Aug. 18, 2003: At ANDA Applicant’s Discretion
– After Aug. 18, 2003: Within 20 Days After ANDA Applicant
Receives Word From FDA That ANDA Is Acceptable to Be
Received
25
Medicare Modernization Act of
2003 -- Impact on Exclusivity
• After December 8, 2003, 180-Day Exclusivity May Be
Forfeited – Section 505(j)(5)(D)
• Grounds for Forfeiture
–
–
–
–
Withdrawal of ANDA
Amendment or Withdrawal of Paragraph IV Certification
Failure to Obtain Tentative Approval Within 30 Months
Collusive Agreement with Another ANDA Applicant, NDA Holder
or Patent Owner
– Expiration of the Patent
– Failure to Market Within 75 Days of: ANDA Approval, 30 Months
Since ANDA Submission, Final Court Decision, Lawsuit Settlement,
Withdrawn Patent
26
Historical Controversies Over
180-Day Exclusivity
•
•
•
•
What is a “Complete” Application?
Must First Filer Be Sued?
Must First Filer “Successfully Defend” Lawsuit?
What is a “Court Decision” That Triggers 180-Day
Exclusivity?
– 1999: FDA Regulation Said Appellate Court
– 1997-2000: Court Rulings Said Trial Court
– 2000: FDA Guidance Said First Court That Decides the Patent Is
Invalid, Unenforceable or Not Infringed
– After Aug. 18, 2003: No Court (Only Trigger Is First Filer’s First
Commercial Marketing)
27
Problems Interpreting
180-Day Exclusivity
• Does Later Filer Ever Get ANDA Exclusivity?
• What About Patents Not Filed Promptly With
FDA (“Late Listed” Patents)?
• Can There Be “Shared” Exclusivity?
– Based on Differing Product Characteristics
– Based on Multiple Patents
– Based on Same-Day Filing of ANDAs
• Can exclusivity be “sold”?
28
Problems Interpreting
180-Day Exclusivity
• Can the ANDA Applicant Force a Patent
Infringement Suit?
– Possibly, via Declaratory Judgment Action
• What Are the Potential Consequences of Settling
the Patent Lawsuit?
– Risk of Lawsuit by Plaintiff ’s Lawyers, Patient Groups,
Shareholders, Competing Generic Companies, FTC
– After Jan. 4, 2004: Must Notify FTC & DOJ Within
10 Business Days of Settlement
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Three slides left …
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Complicated Area
–
Amlodipine Besylate Exclusivity Issues – the FDA Front
•
•
•
•
•
•
Posted: 28 Mar 2007 02:14 PM CDT
The Federal Circuit’s March 22, 2007 decision invalidating Pfizer’s patent on NORVASC (amlodipine besylate), and Mylan’s
commercial launch of its generic version approved under ANDA #76-418 later that day triggering the company’s 180-day
exclusivity period has set off a flurry of activity, both in the courts and at FDA. This case raises several interesting issues about the
availability of 180-day exclusivity once a patent expires and the applicability of pediatric exclusivity. FDA is being asked to address
these issues in three recent citizen petitions submitted to the Agency concerning amlodipine drug products.
Yesterday, the Orange Book Blog reported on the United States District Court for the District of Columbia’s order granting
Mylan’s Emergency Application for a Temporary Restraining Order and/or Preliminary Injunction, in which Mylan argues that “[i]n
the past, the FDA has taken the position that 180-day generic exclusivity does not survive patent expiration [and that there] is no
basis in the Hatch-Waxman Act for such a limitation.” Pursuant to the court’s order, FDA is enjoined from approving any other
ANDAs for generic NORVASC until at least April 13, 2007 at 5:00PM, and after FDA “solicit[s] the views of other interested
parties on this matter by April 4, 2007 [to] render an agency decision on April 11, 2007.” The Federal Circuit also ordered Pfizer
and Mylan “to respond, no later than 10 a.m. on Monday, March 26, 2007, concerning how the invalidity determination affects the
pediatric exclusivity period and the ANDA approval.”
Simultaneous with FDA’s solicitation and consideration of views on this 180-day exclusivity issue, the Agency must now also
consider several citizen petitions concerning amlodipine drug products.
On March 26, 2007, Mylan submitted a petition to FDA (Docket No. 2007P-0116) requesting that FDA stay the approval of any
additional ANDAs for generic amlodipine products until after Mylan’s 180-day exclusivity expires on September 23, 2007. Mylan’s
arguments hew closely to those the company made in its Emergency Application.
On March 21, 2007, Pfizer submitted two petitions (Docket Nos. 2007P-0110 and 2007P-0111) requesting that FDA enforce
pediatric exclusivity rights for amlodipine, and that FDA stay approval of any and all supplements to LOTREL concerning
amlodipine and pediatric exclusivity, respectively. LOTREL is Novartis’s brand name version of the combination of amlodipine
besylate and benazepril hydrochloride. Although Pfizer’s petitions do not concern Mylan’s ANDA approval specifically, they do
raise raise issues concerning the applicability of Pfizer's pediatric exclusivity for amlodipine, and whether the LOTREL NDA is a
505(b)(2) application subject to that exclusivity.
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Generic Tactics – Morphing Into a
“Brand Name” Company
• Teva – Copaxone® -- 1996
• Duramed -- Conjugated Estrogens – Cenestin® -- 1999
– 120 women
– 12 week study
– No animal tox needed
• Par – Megace ES®
– 625/5 ml vs. 40 mg./ml (Bristol Myers)
– Not possible via ANDA Suitability
– But, still only did a bioequivalent study
32
Take Home Messages
• Be Prepared – monitor what’s going on
– FDA Dockets – Petitions
– News
– Your Own Review Documentation – can give hints
•
•
•
•
Be Prepared to Be Aggressive
Anticipate the Unexpected
Know Your Product
Very Complicated Scenarios
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No slides left …
34
Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President, U.S. Pharmaceuticals
THE WEINBERG GROUP INC.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.454.2979
Cell 760.815.4762
D.C. Office 202.730.4123
michael.swit@weinberggroup.com
www.weinberggroup.com
35
About your speaker…
Michael A. Swit, Esq., is Vice President for U.S. Pharmaceuticals at THE WEINBERG GROUP, where he develops
and ensures the execution of a broad array of regulatory and other services to drug and biologics clients seeking to
market products in the United States. His expertise includes FDA and CMS development strategies, compliance and
enforcement initiatives, recalls and crisis management, submissions and related traditional FDA regulatory activities,
labeling and advertising, and clinical research efforts.
Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience
includes serving for three and a half years as corporate vice president, general counsel and secretary of Par
Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial
perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of
FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the
FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the
FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug
Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced
FDA regulatory law with the D.C. office of Burditt & Radzius.
Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial
activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and
editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the
Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored
by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his
law degree from Emory University Law School and is a member of the California, D.C. and Virginia bars.
36
For more than twenty years, leading companies have
depended on THE WEINBERG GROUP when their
products are at risk. Our technical, scientific and regulatory
experts deliver the crucial results that get products to
market and keep them there.
37
38
State Regulation of Clinical Trials
5th National Conference on Managing Legal Risks in Structuring and
Conducting Clinical Trials
American Conference Institute
Boston
September 27, 2006
Michael A. Swit, Esq.
Vice President, Life Sciences
MOST ACTIVE CLINICAL RESEARCH STATES
1.
2.
Top 12 States -- Population1
Top 12 States -- Most Clinical
Studies2
1
California
Maryland (19)
2
Texas
New York
3
New York
California
4
Florida
Texas
5
Illinois
Pennsylvania
6
Pennsylvania
Ohio
7
Ohio
Washington (15)
8
Michigan (13)
Illinois
9
New Jersey (20)
Florida
10
Georgia (19)
Massachusetts (13)
11
North Carolina
North Carolina
12
Virginia (18)
Missouri (17)
http://www.census.gov/population/cen2000/tab04.txt
Compiled from http://www.clinicaltrials.gov Note: # in parens is rank in other column.
40
HOW CAN WE KNOW ALL THE
STATES’ LAWS?
• You can’t (easily)
– One general source: State-by-State Clinical Trial
Requirements Reference Guide, Sept. 2004, Serio, et al.,
Editors, Barnett Educational Services
• Focus on key states -- e.g., see our chart
• Work with your IRBs – they are required to know local
conditions under federal law – thus, protocols and
consents should be tailored by them to meet local
rules
41
California v. Texas -- Age of Consent
California
Texas
Majority – 18
Mental Health Care – 12
Medical Care – 15 or living apart
from parents
Majority – 18, unless disabilities of
minority removed
Mental Health Care & Medical Care –
18, unless 16 and independent,
then can consent to:
♦ infectious disease treatment
♦ pregnancy treatment (but not an
abortion)
♦ substance abuse
42
Consent Process …
California
Texas
Written consent required prior to
administering an experimental drug
(H&S 111525)
No similar explicit rule on
experimental drugs.
But, separate law that hospital
patients have right to be informed
of experimental or research
projects affecting their treatment
43
Consent Process ...
California
Texas
Informed consent must include all
pertinent info, including financial
(Moore v. Regents)
No similar explicit rule on financial
disclosure; but, after Gelsinger,
little question is an implied
obligation to consent process.
Experimental Subjects “Bill of Rights” Not specifically addressed.
– must be provided to subject and
signed before consent to research
H&S § 24172.
44
Consent Process … specifics needed
California
Texas
Must:
Detailed requirements not specifically
addressed in detail.
♦ Sign
♦ Date
♦ Witness
♦ State purpose
♦ State any placebo use
♦ Risks & benefits
♦ Alternatives
♦Recovery time
♦ Withdrawal rights
♦ Name & institution doing study
♦ Sponsor or funding source
♦ Name & address of impartial third-party
contact to complain to
45
Consent Process …
California
Texas
♦ Minors – need parental consent; &
assent of children seven+ years old
Minors – if parent, not available,
others can (e.g., grandparents) per
Tex. Family Code § 32.001
Old law – minor assent to mental
health treatment required; repealed
in 2001
46
Consent Process … specifics needed
California
Texas
Consent relative to Research on Mentally Ill:
Consent relative to Research on Mentally Ill (25
TAC 414.758) – must meet 45 CFR § 46
requirements, plus:
♦ must include any extension of length of stay at
facility
♦ ability to get research drug or device after
research over
♦ use of placebo
♦ if research involves using test article known to be
ineffective for targeted pop.
♦ risk of deterioration
♦ greater requirements if research involves more
than minimal risk:
• independent professional must assess capacity of
individual to consent
♦ consent “must be assessed and enhanced
throughout” the research
♦ If at state hospitals, more requirements apply:
• confidentiality statement
• contact info. For questions, costs & future
findings
♦ To review confidential records of
developmentally disabled person, researcher must
obtain informed consent of subject or LAR
♦ Short form consent is possible (17 CCR 50429)
♦ IRB can authorize waiver of consent in certain
limited circumstances (17 CCR 50427)
47
LEGALLY AUTHORIZED REPRESENTATIVE
California
Texas
Priority Order:
(H&S 24178)
Priority order:
(H&S § 313.004)
♦ Agent via a health care directive
♦ conservator or guardian
♦ spouse
♦ adult child
♦ custodial parent
♦ adult sibling
♦ adult grandchild
♦ closest available adult kin
♦ Spouse
♦ Adult child of patient w/waiver & consent
of all other adult children
♦ Majority of reasonably available adult
children
♦ Parents
♦ Person last ID’d by patient prior to incapacity
♦ Nearest living relative
♦ Member of clergy
Note: if two or more of same priority, if any
objects, NO CONSENT
Note: different order for emergency room use
Note: majority rules if more than one
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LEGALLY AUTHORIZED
REPRESENTATIVE
California
Texas
If LAR involved, informed consent for
research can only be for research related
to the health of the subject (H&S §
24175)
Not addressed specifically
If subject has previously appointed a
health care power of attorney, can
appoint a “surrogate” by personally
informing the supervising health care
provider. If so, surrogate controls over
POA. (H&S § 24175).
Not addressed specifically
49
IRBS
California
Texas
State Dept. of Health Services must
“accept” the IRB; however, if you’re under
a federal assurance, you’re deemed accepted
(H&S § 111540)
Studies on Developmentally Disabled:
IRB must meet 17 CCR 50401:
♦ 5 members
• 1 lay member
• 1 member focused on rights of subjects
• 1 member not affiliated w/facility
♦ Must review protocols within 31 days of
receipt
50
Not specifically addressed; but see below
Studies on Developmentally Disabled:
IRB must meet 25 TAC 414.755(d):
♦ 3 members must know the mental
disorders:
• one professional
• 2 must have been mentally ill or
retarded, or a family member of such, or
an advocate
♦ Facility IRB must be approved by Texas
Dept. of Mental Health’s Office of
Research Admin. (ORA)
RECORDS REQUIREMENTS
California
Texas
♦ Similar
♦ Illegal to disclose medical information
unless compelled by court, law enforcement
agency or patient.
♦ Similar, but also, Covered Entity must:
• document consent
• document waiver OK’d by an IRB or privacy board,
that says:
◘ use of PHI is minimal risk to person
◘ privacy rights will not be adversely affected
◘ privacy risks are reasonable relative to anticipated
research benefits
◘ adequate plan to keep identifiers from being
improperly used
◘ plan to destroy identifiers later
◘ written assurances PHI will not be reused or
disclosed
♦ Disclosure is OK to a P.I. or research
organization for research purposes if patient
ID protected
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RECORDS REQUIREMENTS
California
Texas
♦ Records release forms must be at
least 8 point type and include:
• specific uses
• name of provider
• name of info recipient
• expiry date
Similar rule – Occupations Code §
159.005(b); consent must specify:
• records to be released
• reasons for release
• recipient
♦ Disclosure of lab results via
electronic means is barred
Not specifically addressed
♦ Federal HIPAA overrides state law
(H&S § 130311, as of 9/02)
♦ HIPAA rules essentially apply (H&S §
181.101
52
RECORDS REQUIREMENTS
California
Texas
Pharmaceutical companies (but not
Not specifically addressed
medical device firms) barred:
♦ from disclosing medical information
about a patient without consent.
♦ conditioning receipt of drugs on patient
waiving those rights, except vis-à-vis
enrollment in a clinical study
Developmentally disabled research:
♦ to get access, researcher must sign
confidentiality pledge per 17 CCR 50421
53
Not specifically addressed in this detail.
STATE IND RULES
California
Texas
None explicit.
None explicit.
BUT, cancer research – if not under
a federal IND, must meet several
requirements under H&S § 109325,
including a written statement filed
with state
BUT, to use approved drug for
research, sponsor must submit a copy
of FDA approval letter to Texas
Commissioner of Health
54
EMERGENCY
EXPERIMENTATION
California
Texas
Need for consent for experimental
treatment is exempted if a lifethreatening situation (assumes
incapacity to consent)
Not addressed specifically, except a
psychoactive drug can be
administered without consent to a
resident who is having a
medication-related emergency.
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MENTALLY ILL OR DEVELOPMENTALLY
DISABLED STUDIES
California
Texas
♦ Executive director of state hospital
also must OK research
SAME – 25 TAC 414.754(k)
♦ Other Detailed Requirements:
• researcher duties (17 CCR 50413)
• IRB
Detailed requirements (25 TAC 414.751
et seq.)
♦ adopts Belmont Report
♦ must be a court order for mental
health services in effect before can
approach individual in protective custody
on being involved in research
(25 TAC 414.754(f)
56
MENTALLY ILL OR DEVELOPMENTALLY DISABLED …
California
Texas
No similar requirement relative to
involuntary commitment, but I.C.
rules in H&S § 24170 are similar.
If involuntarily committed:
♦ no placebos
♦ no ineffective doses or medications
♦ if prior studies with 100 or fewer
patients have found minimal or no
proof of safety & effectiveness
57
Research on Prisoners
California
Texas
Inmates have right to choose; I.C. must
include all (from prior slide), and:
♦ right to withdraw
♦ remuneration
NOTE: only applies to behavioral
research
Penal Code § 3502 – bars biomedical
research on prisoners
58
Not addressed specifically.
PRACTICAL ADVICE
• Retain clinical investigators with sophistication in
clinical research; much of state law relates to
practice of medicine
• Start early – requirements are detailed
• FDA (arguably) can cite you for missing a state
requirement – will cite a federal violation (e.g.,
failure to monitor; inadequate consent; IRB not
observing local conditions)
59
PRACTICAL ADVICE …
• If using a CRO, consider those that have local
offices in states you have clinical
• When in doubt, get local counsel!!
Disclaimer: I am not admitted in Texas
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The End
About the speaker …
Michael A. Swit, Esq., who is Vice President, Life Sciences at THE WEINBERG GROUP INC., has
extensive experience in all aspects of FDA regulation with a particular emphasis on drugs and medical
device regulation. In addition to his private legal and consulting experience, Mr. Swit also served for
three and a half years as vice president and general counsel of Pharmaceutical Resources, Inc. (PRI) a
prominent generic drug company and, thus, brings an industry and commercial perspective to his
representation of FDA-regulated companies. While at PRI from 1990 to late 1993, Mr. Swit
spearheaded the company’s defense of multiple grand jury investigations, other federal and state
proceedings, and securities litigation stemming from the acts of prior management. Mr. Swit then served
from 1994 to 1998 as CEO of Washington Business Information, Inc. (WBII) a premier publisher of
FDA regulatory newsletters and other specialty information products for the FDA publishing company.
Before joining THE WEINBERG GROUP, he served in the FDA Regulatory Law Practices at both
Heller Ehrman and McKenna & Cuneo, first in that firm’s D.C. office and then in its San Diego office.
He first practiced FDA regulatory law with the D.C. office of Burditt & Radzius from 1984 to 1988. Mr.
Swit has taught and written on a wide variety of subjects relating to FDA law including, since 1989, codirecting a three-day intensive course on the generic drug approval process, serving on the Editorial
Board of the Food & Drug Law Journal, and editing a guide to the generic drug approval process,
Getting Your Generic Drug Approved, published by WBII. Mr. Swit holds an A.B., magna cum laude,
with high honors in history, in 1979, from Bowdoin College, and earned his law degree from Emory
University in 1982. He is a member of the California, Virginia and District of Columbia bars.
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Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President, Life Sciences
THE WEINBERG GROUP INC.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.633.3501
Cell 760.815.4762
D.C. Office 202.730.4123
michael.swit@weinberggroup.com
www.weinberggroup.com
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For more than twenty years, leading companies have depended on
THE WEINBERG GROUP when their products are at risk.
Our technical, scientific and regulatory experts deliver the crucial
results that get products to market and keep them there.
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